There is limited information on what causes injury to the heart in individuals with Sickle Cell Disease (SCD). Researchers in this study want to see if decreased blood flow to the heart during stress could be causing the heart damage seen in SCD patients. They also want to test people who don't have SCD to see if their hearts react the same way under stress.

Primary Objective

• To estimate the coronary flow reserve (CFR) (also referred to as myocardial perfusion reserve), as measured by PET stress-rest myocardial perfusion imaging, in SCD patients with and without diastolic dysfunction, and healthy controls.

Secondary Objectives

• To investigate the relationship between decreased CFR (quantified with PET stress- rest myocardial perfusion imaging) and presence of abnormal diastolic parameters

This study requires two visits. The first visit includes blood tests, an electrocardiogram (EKG), and an echocardiogram. The second visit includes a positron emission tomography (PET) stress test and a blood test.

Subjects will be considered off-study one week after all post PET imaging study tests have been completed along with the next day and one-week follow-up phone calls are completed.

Inclusion Criteria - Stratum A: Sickle cell patients with diastolic dysfunction

• 18 to 21 years of age
• Black
• Diagnosis of SCD of HbSS and HbSβ0thalassemia genotypes
• Three or more abnormal diastolic parameters (based on guidelines by American Society of echocardiography)

Inclusion Criteria - Stratum B: Sickle cell patients without diastolic dysfunction

• 18 to 21 years of age
• Black
• Diagnosis of SCD of HbSS and HbSβ0thalassemia genotypes
• Two or less abnormal diastolic parameters

Inclusion Criteria - Stratum C: Healthy controls

• 18 to 21 years of age
• Black
• Two or less abnormal diastolic parameters

Exclusion Criteria - Stratum A:

• Recent hospitalization for vaso-occlusive pain crisis or acute chest syndrome in last 4 weeks
• Blood transfusion in the last 3 months
• Individuals with signs, symptoms or EKG findings of acute myocardial ischemia, infarction or unstable angina
• Individuals with history of VT/VF or SVT
• Previous cardiac surgery
• Known congenital heart disease (other than patent ductus arteriosus or Atrial septal defect)
• Stenotic valvular disease or left main coronary artery stenosis
• History of myo/pericarditis
• Left ventricle systolic dysfunction
• Cardiovascular instability/uncontrolled hypertension (h/o hypertensive urgency or emergency)
• History of sinus node dysfunction or high grade AV nodal block
• History of aborted sudden cardiac death or cardiac arrest
• Current seizure disorder on AED
• Pregnant/Breast-feeding
• Any medical or social reason, which, in the opinion of the principal investigators would make the participation of the subject ill-advised.

Exclusion Criteria - Stratum B:

• Diagnosed with three or more abnormal diastolic parameters (based on guidelines by American Society of echocardiography)
• Recent hospitalization for vaso-occlusive pain crisis or acute chest syndrome in last 4 weeks
• Blood transfusion in the last 3 months
• Individuals with signs, symptoms or EKG findings of acute myocardial ischemia, infarction or unstable angina
• Individuals with history of VT/VF or SVT
• Previous cardiac surgery
• Known congenital heart disease (other than patent ductus arteriosus or Atrial septal defect)
• Stenotic valvular disease or left main coronary artery stenosis
• History of myo/pericarditis
• Left ventricle systolic dysfunction
• Cardiovascular instability/uncontrolled hypertension (h/o hypertensive urgency or emergency)
• History of sinus node dysfunction or high-grade AV nodal block
• History of aborted sudden cardiac death or cardiac arrest
• Current seizure disorder on AED
• Pregnant/Breast-feeding
• Any medical or social reason, which, in the opinion of the principal investigators would make the participation of the subject ill-advised.

Exclusion Criteria - Stratum C:

• All genotypes of SCD
• Diagnosed with three or more abnormal diastolic parameters (based on guidelines by American Society of echocardiography)
• Anemia of grade 2 or worse (per CTCAE v5.0) at study visit 1
• Individuals with signs, symptoms or EKG findings of acute myocardial ischemia, infarction or unstable angina
• Individuals with history of VT/VF or SVT
• Previous cardiac surgery
• Known congenital heart disease (other than patent ductus arteriosus or Atrial septal defect)
• Stenotic valvular disease or left main coronary artery stenosis
• History of myo/pericarditis
• Left ventricle systolic dysfunction
• Cardiovascular instability/uncontrolled hypertension (h/o hypertensive urgency or emergency)
• History of sinus node dysfunction or high-grade AV nodal block
• History of aborted sudden cardiac death or cardiac arrest
• Current seizure disorder on AED
• Pregnant/Breast- feeding
• Any medical or social reason, which, in the opinion of the principal investigators would make the participation of the subject ill-advised.

Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

Data will be made available at the time of article publication.

Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.